This project proposes to find ways in which anesthetics disrupt functions of active cells by studying the effects of commonly used anesthetics on model systems. Because excitable cells capable of impulse transmission are among the cell types most affected by anesthetics, neuromuscular transmission is being used as a model synapse. In particular, the isolated in vitro rat diaphram-phrenic nerve preparation will be used to assess anesthetic effects. This system will be perfused with a Ringers type solution with controlled levels of ions and pH. The preparation is kept at a temperature from 20 degrees-40 degrees C by feedback controllers. Anesthetics and neuromuscular blocking drugs are introduced into the system where they equilibrate. The experimental apparatus is capable of measuring the mechanical output of the muscle via a strain guage as well as the electrical depolarization via surface electrodes. Depression of function at the neuromuscular junction is reflected by a change in electrical as well as mechanical response whereas contractile depression affects only the mechanical output. In this way, the known anesthetic depression in this system can be separated into synaptic and membrane effects or contractile effects and the component most sensitive to anesthetic depression can be isolated.